Method of detecting the presence of a biomarker in a sample of a flowable substance and a detector assembly for use in the detection of the biomarker in the sample

ABSTRACT

In the detection of the presence of a biomarker or the like in a sample of a flowable substance, e.g. a powder or a liquid, usually a body fluid, such as blood, urine, or saliva, for example, a disposable sample receiver ( 3 ) is used, which has a receiving chamber ( 301 ) that is dimensioned to receive a predetermined volume and is surrounded by a depression ( 303 ) receiving any excess volume for which there is no room in the receiving chamber ( 301 ). The receiving chamber ( 301 ) has a bottom outlet ( 302 ) closed by a removable strip ( 33 ), e.g. a plastic strip or foil. Upon pulling away the strip ( 33 ) from the bottom outlet, the sample in the receiving chamber is emptied into a flow path ( 32 ) leading to at least one detection compartment ( 321 ) permitting direct visual inspection. Preferably, disposable sample receiver ( 3 ) is used in a detector assembly ( 1 ) including an electronic camera ( 23 ), a CPU ( 26 ) and a display ( 22 ). Hereby, the volume of the sample to be analyzed will always be the same, and by controlling the exact point of time when the sample is passed on into the flow path ( 32 ), a high degree of repeatability and accuracy is achieved, and thereby also a fail-safe system.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to and the benefit of and is acontinuation of U.S. patent application Ser. No. 16/477,143, filed Jul.10, 2019, which United States application is a National StageApplication filed under 35 U.S.C. § 371, of International ApplicationNo. PCT/EP2018/050424, filed Jan. 9, 2018, which internationalapplication further claims priority to and the benefit of SwedishApplication No. 1750028-1, filed Jan. 13, 2017; the contents of all ofwhich as are hereby incorporated by reference in their entireties.

BACKGROUND Related Field

The present invention relates to a method of detecting the presence of abiomarker in a sample of a flowable substance.

Further, it relates to a disposable sample receiver for use in detectionof the presence of a biomarker in a sample of a flowable substance, saiddisposable sample receiver including a receiving chamber for receptionof the sample of flowable substance, a bottom outlet from the receivingchamber, a flow path leading away from the bottom outlet.

In addition, it relates to a detector assembly for use in detection ofthe presence of a biomarker in a sample of a flowable substance, saidassembly including a portable detector housing having a place forreception of a disposable sample receiver, and a disposable samplereceiver adapted to be located in said place.

Related Art

U.S. Pat. No. 9,228,953 B2 (Karlsson et al.) discloses a testing systemfor assessing the level of a biochemical marker, comprising a disposabledevice with a sample inlet and a at least one visible detectioncompartment, provided with composition including a chemical means fordirect detection of said biochemical marker. To assess the level of thebiomarker, the disposable device is placed in a housing that also has asupport surface for a smartphone. After the detection of the biomarker,the smartphone takes a digital picture, which is transmitted viainternet to a server that runs a dedicated program to analyze thepicture and the retransmits the result to the smartphone.

In US '953, the disposable device has a sample inlet in the form of asample inlet connected to a chamber adapted to receive a capillarydevice containing a sample arranged to be placed onto a receivingdevice, e.g. a plasma separation device, i.e. a filter. The disposabledevice is supplied with test blood by means of a capillary device beingfilled with the sample, e.g. a whole blood amounting to 1-100 μl,suitably 25-75 μl, and preferably about 50 μl. However, if desired theblood may be added by a pipette releasing a drop of the sample. Theplasma is made to flow (by negative pressure or by capillary force)through a filter and into a collection chamber, from where it proceedsthrough a microfluidic channel into at least one detection compartmenthaving a volume of 0.1-more preferred 3-10 μl, and most preferred 4-9μl.

BRIEF SUMMARY

The object of the present invention is to provide a fail proof systemfor detection of the presence of a biomarker in a sample of a flowablesubstance.

In a first aspect of the present invention, this object is achieved in amethod of detecting the presence of a biomarker in a sample of aflowable substance, comprising:

-   a) providing a disposable sample receiver having a receiving    chamber, a bottom outlet from the receiving chamber, a flow path    leading away from the bottom outlet;-   b) disposing the sample in the receiving chamber and permitting the    flowable substance to pass through the bottom outlet into the flow    path;-   c) providing a depression surrounding the receiving chamber;-   d) filling the receiving chamber until an excess of the flowable    substance spills over into the depression; and-   e) emptying the receiving chamber by removing from the bottom outlet    a separating member that is impermeable to the flowable substance,    which separating member has prevented flow from the receiving    chamber through the bottom outlet and into the flow path.

By filling the receiving chamber until an excess of the flowablesubstance spills over into the depression, the volume of the sample tobe analyzed will always be the same, and by controlling the exact pointof time when the sample is passed on into the flow path (by removing theseparating member from the bottom outlet of the receiving chamber) ahigh degree of repeatability and accuracy is achieved, and thereby alsoa fail-safe system.

To facilitate the detection, it is preferred that the flow pathcomprises a permeable member, which prevents passage of at least onecomponent of the flowable substance but permits passage of another one.

It is also preferred that the disposable sample receiver comprises adirectly visible detection compartment located at the opposite end ofsaid flow path compared to the bottom outlet, and that the detectioncompartment is provided with a reagent which shifts color upon presenceof a biomarker in the sample of flowable substance.

In the present context, the expression “directly visible detectioncompartment” is to be defined as a detection compartment, which a usercan see from the outside of the sample receiver. This means, as anexample, that a user can inspect the color in the detection compartmentwith the naked eye.

It is to be understood that “a biomarker” is to be interpreted as “atleast one biomarker”. It is further understood that “a biomarker” is ameasurable indicator of some biological state or condition.

Said detection compartment may be prepared with a reagent composition,e.g. arranged to react with one or more of the following biochemicalmarkers, all of which may be present in plasma: LDH, Hemoglobin (Hb),aspartate aminotransferase (AST), alanine aminotransferase (ALT),lactate, Creatinine Kinase (CK), Creatinine, Amylasis (PIA), C-reactiveprotein (CRP), Hydrogen ion concentration (pH), Albumin, K, Mg and Ca.It is to be understood that the examples mentioned above are by no meanslimiting to the basic principles of the invention.

Although the flowable substance usually is a liquid, e.g. various bodyfluids, it could also be a powder. It is expected that in most cases theflowable substance will be blood, and that the permeable member, whichusually is a filter, separates blood cells from plasma containing thebiomarker. Thereby, a simple and accurate detection of the biomarker canbe carried out.

In some cases, it may be desired to control the volume and timing of aflowable substance (i.e. secure that an exact volume is used as well ascontrolling the exact time when said volume is transferred) withoutdetecting a biomarker. For instance this may be the case if the flowablesubstance is in the form of a powder. In such cases, said permeablemember may not be needed.

The detection compartment may or may not be prepared with a reagent.

In some cases, the user may detect a biomarker without the need for anyreagent by merely inspecting the hue of the filter after that a samplehas entered the detection compartment, as is the case e.g. withbilirubin which, if present, will result in the filter acquiring ayellowish color.

An operator may use visual inspection to analyze the color shift, butpreferably the color shift is analyzed by an electronic camera andsoftware, and the result is shown on a display. Thereby it is easy tosave the result for later inspection and/or comparison.

In a second aspect of the present invention, the above object isachieved in that a disposable sample receiver of the kind stated in thesecond paragraph above comprises:

-   a) a depression surrounding the receiving chamber that is    dimensioned to receive a predetermined volume, said depression    receiving any excess volume for which there is no room in the    receiving chamber; and-   b) a removable separating member impermeable to the flowable    substance and disposed at the bottom outlet to keep the bottom    outlet sealed, said separating member upon removal connecting the    receiving chamber to the flow path.

As the receiving chamber is dimensioned to receive a predeterminedvolume and is surrounded by a depression, the receiving chamber can befilled until an excess of the flowable substance spills over into thedepression, whereby the volume of the sample to be analyzed will alwaysbe the same. Further, as the exact point of time when the sample ispassed on to the flow path (by removing the separating member from thebottom outlet of the receiving chamber) can be controlled, a high degreeof repeatability and accuracy is achieved, and thereby also a fail-safesystem.

It is preferred that the disposable sample receiver comprises a directlyvisible detection compartment located at the opposite end of said flowpath compared to the bottom outlet. As pointed out above, in the presentcontext, the expression “directly visible detection compartment” is tobe defined as a detection compartment, which a user can see from theoutside of the sample receiver. This means, as an example, that a usercan inspect the color in the detection compartment with the naked eye.

To facilitate the detection, it is preferred that the flow path at leastupstream of the detection compartment is provided with a permeablemember, which prevents passage of at least one component of the flowablesubstance but permits passage of another one.

Further, it is preferred that a reagent, which shifts color uponpresence of a biomarker, is provided in said flow path, and that thereagent is located in or downstream of the permeable member.

In most cases, said permeable member is a filter member that may includea plurality of individual filters. As pointed out above, although theflowable substance usually is a liquid, e.g. various body fluids, itcould also be a powder. It is expected that in most cases the flowablesubstance will be blood, and that the permeable member, which usually isa filter, separates blood cells from plasma containing the biomarker.Then, the reagent suitably is located in or downstream of the permeablemember. Thereby, matter that might make it difficult to assess the colorshift of the reagent will be prevented from reaching the reagent, and asimple and accurate detection of the biomarker can be carried out.

Then, it is preferable that the permeable member includes an uppermostreceiving filter, at least one separation filter, and a lowermostdetection filter, which contains the reagent and is located in thedetection compartment. Such a filter assembly will prevent any unwantedmatter from reaching the reagent, and any color change looked for willbe easy to ascertain.

The filter/s can be of different types, exemplified but not limited to,blood separation filters, filters for separation by size, filters foraffinity, capture or binding of specific components in the fluid to befiltered. The filters may be made of natural or synthetic material, or acombination thereof, and be of symmetric or asymmetric type.

In a third aspect of the present invention, the above object is achievedin that in a detector assembly of the kind stated in the third paragraphabove said disposable sample receiver comprises:

-   a) a receiving chamber for reception of the sample of flowable    substance, a bottom outlet from the receiving chamber, a flow path    leading away from the bottom outlet, and in the flow path at least    one of a reagent, which shifts color upon presence of the biomarker,    and a permeable member, which prevents passage of at least one    component of the flowable substance but permits passage of another    one, said disposable sample receiver further comprising:    -   aa) a depression surrounding the receiving chamber that is        dimensioned to receive a predetermined volume, said depression        being adapted to receive any excess volume for which there is no        room in the receiving chamber; and    -   ab) a removable separating member impermeable to the flowable        substance and disposed at the bottom outlet to keep the bottom        outlet sealed, said separating member upon removal from the        bottom outlet connecting the receiving chamber to the flow path;        and-   said detector housing comprises:-   b) a device for removing the separating member from the bottom    outlet of the receiving chamber to activate the disposable sample    receiver.

As the receiving chamber is dimensioned to receive a predeterminedvolume and is surrounded by a depression, the receiving chamber can befilled until an excess of the flowable substance spills over into thedepression, whereby the volume of the sample to be analyzed will alwaysbe the same. Further, as the detector housing comprises a device forremoving the separating member from the bottom outlet of the receivingchamber, the exact point of time when the sample is passed on to thereagent (by removing the separating member from the bottom outlet of thereceiving chamber) can be controlled, a high degree of repeatability andaccuracy is achieved, and thereby also a fail-safe system.

It is preferred that the disposable sample receiver comprises a directlyvisible detection compartment located at the opposite end of said flowpath compared to the bottom outlet. As pointed out above, in the presentcontext, the expression “directly visible detection compartment” is tobe defined as a detection compartment, which a user can see from theoutside of the sample receiver. This means, as an example, that a usercan inspect the color in the detection compartment with the naked eye.

To facilitate the detection, it is preferred that the flow path at leastupstream of the detection compartment is provided with a permeablemember, which prevents passage of at least one component of the flowablesubstance but permits passage of another one.

Further, it is preferred that a reagent, which shifts color uponpresence of a biomarker, is provided in said flow path, and that thereagent is located in or downstream of the permeable member.

The permeable member suitably is a filter member that may include aplurality of individual filters. Further, although the flowablesubstance usually is a liquid, e.g. various body fluids, it could alsobe a powder. It is expected that in most cases the flowable substancewill be blood, and that the permeable member, which usually is a filter,separates blood cells from plasma containing the biomarker. Then, thereagent suitably is located in or downstream of the permeable member.Thereby, matter that might make it difficult to assess the color shiftof the reagent will be prevented from reaching the reagent, and a simpleand accurate detection of the biomarker can be carried out.

Then, it is preferable that the permeable member includes an uppermostreceiving filter, at least one separation filter, and a lowermostdetection filter, which contains the reagent. Such a filter assemblywill prevent any unwanted matter from reaching the reagent.

Even though the color shift of the reagent can be assessed by visualinspection, it is preferred that the detector housing comprisesequipment for analyzing color change marks of the biomarker to bedetected, and said equipment includes an electronic camera, software,and a display for displaying the result of the analysis. Thereby it iseasy to save the result for later inspection and/or comparison.

Suitably, the disposable sample receiver includes a top member and abottom member. Further, the top member has wall portions defining sidewalls of the receiving chamber, and the removable separating member isan elongate strip having one end closing the bottom outlet by forming abottom of the receiving chamber and the other end fixed to a bodyportion of the disposable sample receiver. In addition, the disposablesample receiver has an internal support for the strip, and the internalsupport is spaced from the fixed end of the strip to form between them aspace under the strip. The space has a depth that is sufficient topermit the strip to be pressed into the space a distance that will pullthe strip away from the bottom outlet to empty the sample of flowablesubstance into the flow path. Thereby, a simple and reliable mechanismfor opening the bottom outlet of the receiving chamber at anidentifiable point of time is obtained.

It is preferred that the top member of the disposable sample receiverhas an opening located above the space, and that a device for pullingthe sealing end of the strip away from the bottom outlet includes apivotal member on the detector housing provided with a protrusionadapted to enter the opening in order to press down the strip to removeit from the bottom outlet and thereby let the flowable substance flowinto the flow path.

Suitably, the pivotal member is a lid that on shutting will cover thedisposable sample receiver and simultaneously pull away the strip fromthe bottom outlet to let the sample of flowable substance flow into theflow path, whereby every sample to be analyzed will be subjected to thesame testing conditions with regard to volume and timing.

BRIEF DESCRIPTION OF THE FIGURES

In the following, the invention will be described in more detail withreference to preferred embodiments and the appended drawings.

FIG. 1 is an isometric view of a preferred embodiment of a detectorassembly of the invention, including a detector housing and a disposablesample receiver.

FIG. 2 is an isometric view of the detector assembly of FIG. 2 from aslightly different angle and with a portion of the housing madetransparent for showing its interior.

FIG. 3 is an isometric view of a top member of the disposable samplereceiver of FIG. 1.

FIG. 4 is an isometric view of a bottom member of the disposable samplereceiver of FIG. 1 and also shows an exploded view of a filter assemblythat may be located in the bottom member.

FIG. 5 is a schematic longitudinal cross-sectional view of thedisposable sample receiver of FIG. 1 showing inter alia a removableseparating member in the shape of a strip having one end fixed to thereceiver body and the other end sealing against a bottom outlet of achamber for receiving the sample.

FIG. 6 is a view similar to FIG. 5 but showing how the removableseparating member is removed from the bottom outlet to open the bottomoutlet, so that the receiving chamber is emptied and part of the samplehas arrived at the reactant for detection of the biomarker.

FIG. 7 is a longitudinal cross-sectional view of the top member of thedisposable sample receiver of FIG. 1 showing a depression surroundingthe receiving chamber.

FIG. 8 is a view of the underside of the bottom member of the disposablesample receiver of FIG. 1 showing a transparent window for inspection ofa change of color in the reactant.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

The detector assembly 1 shown in FIG. 1 is a preferred embodiment of thepresent invention and is adapted for use in detection of the presence ofa biomarker in a sample of a flowable substance, which usually is a bodyfluid, such as whole blood, urine, and saliva, for example. The assembly1 includes a portable detector housing 2 having a place 25 for receptionof a disposable sample receiver 3. It further includes a disposablesample receiver 3 adapted to be located in said place 25.

The disposable sample receiver 3 has a top member 30 shown in FIG. 3 anda bottom member 31 shown in FIG. 4. The top member 30 fits tightly onbottom member 31. FIG. 8 shows that the bottom member 31 on the outsideof its wall has a plurality of locking projections 316, which areadapted to cooperate with a corresponding number of locking indentations306 on the inside of the wall of the top member 30 shown in FIG. 7.Together, the projections 316 and the indentations 306 form snap locks.As is best shown in FIGS. 5-7, the top member 30 has a receiving chamber301 for reception of the sample of flowable substance, and a bottomoutlet 302 from the receiving chamber 301. When the top member 30 isfixed on the bottom member 31, a flow path 32 leading away from thebottom outlet 302 is defined between the top member 30 and the bottommember 31. A depression 303 surrounds the receiving chamber 301 that isdimensioned to receive a predetermined volume. The depression 303 isadapted to receive any excess volume for which there is no room in thereceiving chamber 301. Thereby the analyzed amount of the sample isexactly the same each time an analysis is carried out.

As is best shown in FIGS. 5 and 6, the disposable sample receiver 3further has a removable separating member 33 that is impermeable to theflowable substance and disposed at the bottom outlet 302 to keep thebottom outlet 302 sealed. Upon removal separating member 33 from thebottom outlet 302, the receiving chamber 321 is connected to the flowpath 32, at the end of which a detection compartment 321 is located. Inthe embodiment shown in FIGS. 5 and 6, the detection compartment 321 isformed by a recess in the bottom member 31. If desired, the flow path 32may split into a plurality of branches (not shown) and every branch hasits own separate detection compartment 321.

In the preferred embodiment shown in FIGS. 5 and 6, the removableseparating member 33 is an elongated strip, which according to one,non-limiting example is a substantially T-shaped plastic foil. One end332 of the strip or foil 33 closes the bottom outlet 302 by forming abottom of the receiving chamber 301, and the other end 331, i.e. the topportion of the “T”, is fixed to a body portion 305, 312 of thedisposable sample receiver 3. In the preferred embodiment shown in FIGS.4-6, the body portion 312 is formed by three posts extending upward fromthe bottom of the bottom member 31. The top of each post 312 has areduced diameter, and the fixed end 333 of the removable strip or foil33 has three matching holes for securing the fixed end 331 of the stripor foil 33 to the tops of the posts 312. To secure the strip or foil 33to the posts 312, the top member 30 suitably is provided internally withthree sockets 305 adapted to fit on the tops of the three posts 312.

Said elongated strip 33 may be of various materials, however accordingto one example it is made of 12 μm thick Hostaphan® WN from “Mitsubishipolyester film”, which is a translucent white film made of polyester,e.g. polyethylene terephthalate (PET) with high dielectric strength andlarge volume resistance and which can be easily formed in both warm andcold states.

Another conceivable example is 0.19 μm thick Mylar® Apolyethyleneterephtalate-based transparent, flexible polyester film fromSynflex, which is impervious to moist and solvents.

Both of the above examples of suitable materials for said elongatedstrip 33 provides impervious, yet flexible and pliable film materialswhich both prevents the flowable substance from exiting via the outlet302, and also is flexible enough to be pulled away from the outlet. Theskilled person understands that the above mentioned materials are merelytwo examples out of many, and that many other kinds of materials may beequally suitable for said elongated strip 33. The pulling away of thestrip from the outlet will now be described in more detail.

FIGS. 4-6 also show that the bottom member 31 of the disposable samplereceiver 3 further has an internal transversal support 311 for the strip33. The internal support 311 is spaced from the fixed end 331 of thestrip or foil 33 to form between them a space 313 under the strip orfoil 33. The space 313 has a depth that is sufficient to permit thestrip or foil 33 to be pressed into the space 313 a distance that willpull the sealing end 332 of the strip or foil 33 away from the bottomoutlet 302 in order to empty the sample of flowable substance into theflow path 32 as illustrated in FIG. 6. As shown in FIG. 4, it ispreferred that the internal support 311 is a transversal wall having atits top a recess 315 of a width and a depth that makes it suitable forguiding the strip or foil 33. Preferably, the strip or foil 33 is of athickness that is sufficient to make it self-supporting but yet pliableenough to be pressed down into the space 313 to open the bottom outlet302.

To press the strip or foil 33 into the space 313 as shown in FIG. 6, itis preferred that the top member 30 of the disposable sample receiver 3has an opening 304 located above the space 313. Then, as shown in FIG.1, it is also preferred that a device for pulling the sealing end 332 ofthe strip or foil 33 away from the bottom outlet 302 of the receivingchamber 301 includes a pivotal member 21 located on the detector housing2 and provided with a protrusion 211 adapted to enter the opening 304 inorder to press down the strip or foil 33 to remove it from the bottomoutlet 302 and thereby let the flowable substance flow into the flowpath 32.

In the preferred embodiment shown in FIG. 1, the pivotal member is a lid21 that on shutting will cover the disposable sample receiver 3 andsimultaneously pull away the strip 33 from the bottom outlet 302 to letthe sample of flowable substance flow into the flow path 32, wherebyevery sample to be analyzed will be subjected to the same testingconditions with regard to volume and timing. Further, in the embodimentshown in FIG. 1 the detector assembly 1 has a separate pivotal locatinglid 24 mounted under lid 21. As is best shown in FIG. 2, the locatinglid 24 has an opening of a shape that matches the outer contour of thedisposable sample receiver 3 to hold the sample receiver in an exactpredetermined position on place 25, which in the shown embodiment isrectangular and larger than the disposable sample receiver 3.

At least upstream of the detection compartment 321, the flow path 32preferably is provided with a permeable member 4, which prevents passageof at least one component of the flowable substance but permits passageof another one. In most cases said permeable member 4 suitably is afilter member that may include a plurality of individual filters. Aspointed out above, although the flowable substance usually is a liquid,e.g. various body fluids, it could also be a powder. It is expected thatin most cases the flowable substance will be blood, and that thepermeable member 4, which usually is a filter, separates blood cellsfrom plasma possibly containing a biomarker. If desired, the permeablemember 4 may be a single filter member, for example. However, in thepreferred embodiment of FIG. 4 it is a filter assembly 4 shown in anexploded view and comprising an uppermost receiving filter 40, at leastone separation filter 41, and lowermost detection filter 42 that isadapted to be located in the detection compartment 321. As shown in FIG.4, an end portion of the detection compartment 321 may be wider than thelowermost detection filter 42 to receive the component of the flowablesubstance that has passed through the entire filter assembly 4. Thedetection compartment 321 has a stop 322 to assist in the correctpositioning of the lowermost detection filter 42. The filter assembly 4has such a thickness that when it is placed in position in thedisposable sample receiver 3, it will press the removable strip or foil33 sealingly against the bottom outlet 302 of the receiving chamber 301,but yet permit the protrusion 211 of the pivotal lid 21 to pull theremovable strip or foil 33 away from the bottom outlet to empty thereceiving chamber 301 on the closing of the lid 21.

A reagent, which shifts color upon presence of the biomarker, may beprovided in the flow path 32 and is then located in or downstream of thepermeable member 4. When present, it is always located in the detectioncompartment 321, suitably in the lowermost detection filter 42 if such aone is provided.

To make a color shift in the detection compartment 321 directly visible,the bottom member 31 of the disposable sample receiver 3 may betransparent or just have a transparent portion 314 right under thedetection compartment 321 as shown in FIG. 8. If desired, also the topmember 30 may be made of transparent material. To assist the user of thedetector assembly 1 in assessing any possible color shift in thedetection compartment 321, it is preferred that the detector housing 2as shown in FIG. 2 comprises an electronic camera 23 for taking a photoof the detection compartment 321 through the transparent portion 314 ofthe bottom member 31. The detector housing 2 further comprises a CPU 26,a display 22 and generally also at least one USB port 27. The photo istransmitted to the CPU 26, which after processing the data passes themon to the display 22. Preferably, a sensor (not shown) senses theclosing of the lid 21 and sends a signal to the CPU 26 to start a timerwhen the lid protrusion 211 pulls away the removable strip or foil 33from the bottom outlet 302 to empty the receiving chamber 301.

In this way, the exact point of time when the sample is passed on to thereagent (by removing the separating member 33 from the bottom outlet 302of the receiving chamber 301) can be controlled, in combination with thedepression 303 that is adapted to receive any excess volume for whichthere is no room in the receiving chamber 301 so that the analyzedamount of the sample is exactly the same each time an analysis iscarried out, a high degree of repeatability and accuracy is achieved,and thereby also a fail-safe system.

Many modifications and other embodiments of the inventions set forthherein will come to mind to one skilled in the art to which theseinventions pertain having the benefit of the teachings presented in theforegoing descriptions and the associated drawings. Therefore, it is tobe understood that the inventions are not to be limited to the specificembodiments disclosed and that modifications and other embodiments areintended to be included within the scope of the appended claims.Although specific terms are employed herein, they are used in a genericand descriptive sense only and not for purposes of limitation.

The present invention is applicable for use in detection of the presenceof a biomarker or the like in a sample of a flowable substance, e.g. apowder or a liquid, usually a body fluid, such as blood, urine, orsaliva, for example.

1. A method of detecting the presence of a biomarker in a sample of aflowable substance, said method comprising the steps of: providing adisposable sample receiver (3) having a receiving chamber (301), abottom outlet (302) from the receiving chamber (301), a flow path (32)leading away from the bottom outlet (302); disposing the sample in thereceiving chamber (301) and permitting the flowable substance to passthrough the bottom outlet (302) into the flow path (32); providing adepression (303) surrounding the receiving chamber (301); filling thereceiving chamber (301) until an excess of the flowable substance spillsover into the depression (303); placing the disposable sample receive(3) in a place (25) of a detector assembly (1); and emptying thereceiving chamber (301) by closing of a lid (21) of the detectorassembly (1), thereby passing a protrusion (211) provided on the lid(21) through an opening (304) of the disposable sample receiver (3) tocause the flowable substance to flow from the receiving chamber (301)through the bottom outlet (302) and into the flow path (32)
 2. A methodas claimed in claim 1, wherein said flow path (32) comprises a permeablemember (4), which prevents passage of at least one component of theflowable substance but permits passage of another one.
 3. A method asclaimed in claim 2, wherein said disposable sample receiver (3)comprises a directly visible detection compartment (321) located at theopposite end of said flow path (32) compared to the bottom outlet (302),wherein said detection compartment (321) is provided with a reagentwhich shifts color upon presence of a biomarker in the sample offlowable substance.
 4. A method as claimed in claim 1, wherein saiddisposable sample receiver (3) comprises a directly visible detectioncompartment (321) located at the opposite end of said flow path (32)compared to the bottom outlet (302), wherein said detection compartment(321) is provided with a reagent which shifts color upon presence of abiomarker in the sample of flowable substance.
 5. A method as claimed inclaim 2, wherein the flowable substance is whole blood, and thepermeable member (4) separates blood cells from plasma containing thebiomarker.
 6. A method as claimed in claim 3, wherein the flowablesubstance is whole blood, and the permeable member (4) separates bloodcells from plasma containing the biomarker.
 7. A method as claimed inclaim 5, wherein the reagent is located in or downstream of thepermeable member (4).
 8. A method as claimed in claim 3, wherein thereagent is located in or downstream of the permeable member (4).
 9. Amethod as claimed in claim 8, further comprising the steps of: analyzingthe color shift by an electronic camera (23) and software (in 26), andshowing the result on a display (22).
 10. A detector assembly (1) foruse in detection of the presence of a biomarker in a sample of aflowable substance, said assembly (1) comprising: a portable detectorhousing (2) having a place (25) for reception of a disposable samplereceiver (3), and a disposable sample receiver (3) configured to belocated in said place (25), said disposable sample receiver (3)comprising: (i) a receiving chamber (301) for reception of the sample offlowable substance, a bottom outlet (302) from the receiving chamber(301), a flow path (32) leading away from the bottom outlet (302); and(ii) a depression (303) surrounding the receiving chamber (301) that isdimensioned to receive a predetermined volume, said depression (303)receiving any excess volume for which there is no room in the receivingchamber (301); and wherein said detector housing (2) comprises a lid(21), provided with a protrusion (211) to activate the disposable samplereceiver (3), whereby the sample of flowable substance enters the flowpath (32).
 11. A detector assembly (1) as claimed in claim 10, whereinsaid disposable sample receiver (3) comprises a directly visibledetection compartment (321) located at the opposite end of said flowpath (32) compared to the bottom outlet (302.
 12. A detector assembly(1) as claimed in claim 11, wherein the detector housing (2) comprisesequipment for analyzing color change marks of the biomarker to bedetected, said equipment including an electronic camera (23), software(in 26), and a display (22) for displaying the result of the analysis.13. A detector assembly (1) as claimed in claim 10, wherein the detectorhousing (2) comprises equipment for analyzing color change marks of thebiomarker to be detected, said equipment including an electronic camera(23), software (in 26), and a display (22) for displaying the result ofthe analysis.